Antiangiogéniques et métastases cérébrales: plus de peur que de mal ?

Brain metastases occur in 5% to 20% of cancer patients, depending on the primary tumor type. Several angiogenesis inhibitors have shown clinical efficacy in numerous tumors that frequently metastasize to the brain. However, clinical trials of such angiogenesis inhibitors have excluded patients with brain metastases owing to the theoretical risk of cerebral hemorrhage. Therefore, the available safety data are mainly retrospective: cerebral hemorrhage incidence is estimated to affect 0.1% to 3% of patients treated with angiogenesis inhibitors. Efficacy data are scarce, but case reports of brain metastases with complete and partial responses have been published. Few retrospective reports with few patients suggest that radiation therapy or radiosurgery could be safe. Therefore, available safety data suggest that angiogenesis inhibitor can be used to treat cancer patients with brain metastases. Prospective evaluation is warranted, and cancer patients who harbor brain metastases should not be systematically excluded from prospective clinical trials evaluating angiogenesis inhibitors.     

Occult Contralateral Lateral Lymph Node Metastases in Unilateral N1b Papillary Thyroid Carcinoma

World Journal of Surgery - Therapeutic lateral neck dissection (ND) is recommended for N1b papillary thyroid carcinoma (PTC), while prophylactic contralateral lateral ND is not. Given the paucity...     

American association for cancer research — AACR congress 2014

This year the American association for cancer research meeting was held in San Diego. “Harnessing breakthroughs and targeting cures” was the title of this meeting where the major recent scientific data on cancer research were discussed. This year was undoubtedly the year of immunotherapy and immunology of tumors. With the aim of sharing the data presented at this congress, AERIO (Association d’Enseignement et de Recherche des Internes d’Oncologie) and Oncologie joined to propose a digest of this outstanding congress. Of course, exhaustivity is not an objective of this type of digest which reflects the choices of young researchers and physicians, with the help of the editorial board, among the multiple themes and researches presented and discussed during this meeting. Tumor immunology and immunotherapy data from the congress are reported. Moreover, autophagy, microbiome, liquid biopsy, tumoral heterogeneity, and cancer stem cells data from this congress are reported, as a reflection of the diversity of this meeting and cancer research. From a clinical point of view, new targets and molecules and the new design of clinical trial are also reported.     

Challenging pre-surgical localization of hyperfunctioning parathyroid glands in primary hyperparathyroidism: the added value of <Superscript>18</Superscript>F-Fluorocholine PET/CT

Purpose

To evaluate the added value of ¹⁸F-Fluorocholine (¹⁸F-FCH) PET/CT in presurgical imaging of patients with primary hyperparathyroidism (HPT) and challenging localization of the hyper-functioning parathyroid glands.

Methods

We included 27 consecutive patients with primary HPT (19 F; median age: 58 years), with either (i) non-conclusive pre-surgical localization with ⁹⁹mTc-sestaMIBI scintigraphy and neck ultrasonography (US), (ii) recurrence of previously operated HPT, or (iii) familiar HPT with a suspicion of multiple gland disease. Histological findings and resolution of HPT were considered as the gold standard.

Results

¹⁸F-FCH PET/CT was positive in 24/27 patients. Twenty-one patients underwent surgery with 27 resected lesions (14 adenomas, 11 hyperplastic glands, two hyper-functioning histologically normal glands), with resolution of HPT in 19/21 patients (90%). ¹⁸F-FCH PET/CT localized 22 lesions in 17/21 patients (per patient: sensitivity 81%, positive predictive value (PPV) 94%; per gland: sensitivity 76%, PPV 85%, specificity 91%, negative predictive value (NPV) 86%). ¹⁸F-FCH PET/CT found eight lesions which were undetectable on both ⁹⁹mTc-sestaMIBI scintigraphy and US. In patients with a familial HPT and/or a multiple gland disease, sensitivity was 100 and 79% on a per-patient and a per-gland analysis respectively, while NPV was 63%. In six patients with a persistence or recurrence of previously treated HPT, ¹⁸F-FCH PET/CT localized all lesions, both in sporadic and familiar disease.

Conclusions

¹⁸F-FCH PET/CT is a promising modality in challenging pre-surgical localization of hyper-functioning parathyroid glands, such as inconclusive standard imaging, recurrence after surgery, or suspected multiple gland disease.

     

Characterization,Prognosis, and Treatment of Patients With Metastatic Lung Carcinoid Tumors

IntroductionMetastatic lung carcinoids (MLCs) remain poorly characterized and no prognostic stratification exists.MethodsWe conducted a retrospective study including patients with MLCs in two European expert centers. The aims were to characterize these cases and to identify prognostic factors of survival and effectiveness of their treatments.ResultsA total of 162 patients with MLC were included: 50% were women, and the median age was 61 years. Half of the patients had synchronous metastases, mainly located in the liver (75%), bone (42%), and lung (25%). According to WHO classification, MLCs were typical (28%), atypical (60%), or unspecified (12%). A functioning syndrome was observed in 43% of cases and an uptake at somatostatin receptor scintigraphy in 76% of cases. The 5-year overall survival rate was 60% and at 10 years this was 25%. In multivariate analysis, Eastern Cooperative Oncology Group performance status of 0-1 (hazard ratio [HR]: 5.81, 95% confidence interval [CI]: 2.10–16.11), uptake on SRS (HR: 0.38, 95% CI: 0.22–0.66), low serum chromogranin A (HR: 2.27, 95% CI: 1.36–3.81), and typical carcinoid (HR: 1.87, 95% CI: 1.26–2.78) were associated with better survival. According to Response Evaluation Criteria in Solid Tumors version 1.0, the highest objective response rates were obtained after radiofrequency ablation of metastases (86%), liver embolization (56%), peptide receptor radionuclide therapy (27%), and oxaliplatin-based chemotherapy (18%).ConclusionsMLCs are characterized by a high frequency of atypical carcinoids, functioning syndrome, and liver/bone metastases. WHO classification, performance status, somatostatin receptor scintigraphy, and chromogranin A were associated with longer survival. Partial response was more frequent with locoregional therapies, peptide receptor radionuclide therapy, or oxaliplatin-based chemotherapy.     

Interferon-alpha Treatment for Disease Control in Metastatic Pheochromocytoma/Paraganglioma Patients

Interferon-alpha (IFN-alpha) is recommended in neuroendocrine tumors (NET). Malignant pheochromocytoma and paragangliomas (MPPGLs) constitute a rare subgroup of NET with few treatment options. IFN-alpha efficacy in patients with MPPGLs was evaluated in a single-center retrospective study. Progression-free survival (PFS) was the primary endpoint according to RECIST 1.1 and/or PERCIST 1.0, and response rate, safety, and symptomatic efficacy were secondary endpoints. Fourteen patients received peginterferon alfa-2a (90 to 180 μg/week) or interferon alfa-2b (1.5 to 3 million units × 3/week) at our institution between December 2005 and February 2014 as the first (n = 7), second (n = 3), or subsequent line (n = 4) of treatment. Most of the patients had a slowly progressive disease before IFN-alpha initiation. Eight patients were men (57%); the median age was 44. At the beginning of treatment, 12 patients had progressive disease demonstrated by FDG-PET (n = 9), MIBG (n = 1), or CT scan (n = 2). Most of the patients treated (64%) had metastatic disease limited to or predominantly located in the bones. During IFN-alpha therapy, bone-directed loco-regional treatments were performed in 9 patients (range 1–4). Median PFS was 17.2 months (95% CI [12.1–58.3]). We observed 3 partial metabolic responses, 9 stable diseases, and 2 progressive diseases. No partial response according to RECIST 1.1 was observed. Symptomatic relief of pain, headaches, diarrhea, or sweating occurred in 6 out of 10 symptomatic pts. Most frequent all grade IFN-α-related toxicities were asthenia (n = 10), lymphopenia (n = 7), thrombopenia (n = 6), and anemia (n = 5). Median overall survival was 7.5 years (95% CI [4–NR]). This study suggests symptomatic response and tumor control effect with interferon-alpha in progressive MPPGLs.     

Exploring Reticular Pseudodrusen Extent and Impact on Mesopic Visual Sensitivity in Intermediate Age-Related Macular Degeneration

PurposeTo explore the impact of the extent of reticular pseudodrusen (RPD) on mesopic visual sensitivity in individuals with intermediate age-related macular degeneration (AMD).MethodsIn total, 570 eyes from 285 participants with bilateral large drusen underwent microperimetry testing to assess the visual sensitivity of the central 3.6-mm region and multimodal imaging to determine the extent of RPD in the central 20° × 20° region (at the eye level). Mean visual sensitivity within five sectors in the central 3.6-mm region sampled on microperimetry and the extent of RPD in these sectors were derived. Linear mixed models were used to examine the association between the extent of RPD on overall mean visual sensitivity and sector-based mean sensitivity.ResultsAn increasing extent of RPD at the eye level and within sectors was associated with a significant reduction in overall and sector-based mean sensitivity, respectively (P < 0.001 for both). However, when both RPD parameters were considered together in a multivariable model, only an increasing extent of RPD at the eye level (P < 0.001) and not within each sector (P = 0.178) was independently associated with reduced sector-based mean sensitivity.ConclusionsMesopic visual sensitivity is generally reduced in eyes with large drusen and coexistent RPD compared to eyes without RPD, with greater reductions with an increasing extent of RPD. However, reduced sector-based visual sensitivities are explained by the overall extent of RPD present, rather than their extent within the sector itself. These findings suggest that there are generalized pathogenic changes in eyes with RPD accounting for the observed mesopic visual dysfunction.